Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

Abstract

Background Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Methods Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. Results Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. Conclusions These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

New Insights on Acanthus ebracteatus Vahl: UPLC-ESI-QTOF-MS Profile, Antioxidant, Antimicrobial and Anticancer Activities

“…The results from our study suggested that AEL-sed showed reasonable anticancer effects. Several phytochemicals, such as diosmetin, esculetin, isoacteoside, baicalin, isoamericanol A, luteolin, apigenin, and genkwanin, among several others identified in the extract, have been reported as promising anticancer agents in several in vitro and in vivo studies [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Therefore, A. ebracteatus extract contains several constituents with promising bioactivities that could be beneficial for the treatment of several disorders.…”

High Concentrations of Genistein Decrease Cell Viability Depending on Oxidative Stress and Inflammation in Colon Cancer Cell Lines

“…The increase in the sub G 0 /G 1 phase was previously seen by Salti and collaborators in the HT29 cells with a treatment with GEN 100 µM for 72 h [ 29 ]. In contrast, SW620 cells presented a G 2 /M cell cycle arrest of more than 85% of the cells, which could explain the decrease in cell viability due to the inability of SW620 cells to divide, causing a cytostatic effect of GEN on this cell line [ 30 ].…”

BP‑1‑102 exerts antitumor effects on T‑cell acute lymphoblastic leukemia cells by suppressing the JAK2/STAT3/c‑Myc signaling pathway

“…c-Myc is a downstream gene regulated by STAT3. The STAT3/c-Myc axis is involved in the oncogenesis, progression, metabolism and therapeutic response of a variety of cancers (34)(35)(36)(37). Haizhi Yu et al found that c-Myc expression levels were increased in patients' T-ALL cells as well as Jurkat and DU528 T-ALL cell lines compared with peripheral blood mononuclear cells (PBMCs) from healthy donors (21).…”